The objectives are to continue to study the site of action of inhibitors and their mode of inhibition. In studies using the Sperber chicken preparation, it has been shown that novobiocin like probenecid blocks the transport of certain organic acids at the peritubular membrane of the renal tubular cell. Furthermore it appears that transport of organic bases may also be carried out at the peritubular membrane. Emphasis will be placed on experimentally substantiating this latter site of transport. The model system we have developed is holding up well to close scrutiny and we will continue to develop new drug- metabolite pairs to test the model. Thereby, we will be able to indicate other sites of action of various types of inhibitors. On the liver, a new technique, retrograde intrabiliary injection, has been developed to study the processes of absorption of compounds from the bile and reexcretion of metabolites into bile. Further development of this technique will provide a unique approach to studying hepatic function. Marker substances being studied are inulin, morphine, mannitol, sulfobromophthalein, ouabain to name a few. Effects of changes in bile duct occlusion time and hepatotoxic agents will be studied.